Activities of the principal brain vesicular monamine transporter, VMAT2, are key to understanding the cellular compartmentalization of monoamines that may play a key role in modulating the actions and neurotoxicities induced by amphetamine and by each of the toxins that selectively kills dopaminergic neurons to provide the best current models of Parkinsons disease. In this year, workers in this Branch continued to describ the properties of knockout mice with deletions of the VMAT2 gene. EKG monitoring revealed a good correlation betwen the sudden death experiences by some VMAT2 deficient heterozygote mice and prolonged QT intervals. Aging studies documented clear reductions in locomotion and in amphetamine responsiveness. Mice with deletions of VMAT2 and the plasma membrane transporters DAT and SERT are viable and fertile. VMAT2 knockout mice continue to substantially enhance our understanding of mechanisms of age interactions with psychostimulants, locomotor systems and mechanisms apparently predisposing to fatal cardiac arrythmias. - amphetamine Parkinson's disease Age Cardiac arrythmias - Human Subjects: Interview, Questionaires, or Surveys Only